This project will study rat intestinal epithelial cell glycosyltransferases and cell membrane glycoproteins to determine their role in the control of differentiation. Methods have been established which separate the differentiated villus cell from the undifferentiated crypt cell. Furthermore, intestinal plasma membranes have been purified and separated from a purified Golgi fraction. New data indicate a dissociation between protein synthesis and glycosylation of membrane proteins, suggesting considerable post-translational modifications during villus cell membrane synthesis. We intend to continue to analyze and characterize the changes in intestinal epithelial cell surface membrane glycoproteins and their synthesis associated with cell turnover, differentiation, and tumor induction. We also will continue our studies on the role of galactosyltransferase activity in moderating cell growth in tissue culture. Recent work has demonstrated that UDP-galactose inhibits cell growth and that the mechanism of inhibition requires culture medium calf serum galactosyltransferase activity. This inhibition of cell growth appears to be due to an alteration of cell surface glycoconjugates. We intend to: (1)\isolate and characterize the galactosyltransferase activity responsible; (2)\isolate and characterize the cell surface molecule(s) that affects cell division when galactose is added to its oligosaccharide; and (3)\determine the intracellular mechanism by which UDP-galactose arrests cell division. Differences among normal, tumor, and metastatic-potent cell lines will be compared. It is hoped that these studies will further define the cell membrane changes peculiar to tumor growth and the ability of a tumor cell to metastasize. (A)